AMBITION: A Multicenter Single-arm P2 to Evaluate Safety and Efficacy of the Total Neoadjuvant Therapy for cT2 Rectal Cancer

Sponsor

Osaka University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05939661

Collaborator

(none)

Enrollment

Locations

Arm

82.2

Anticipated Duration (Months)

22.5

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A multicenter single-arm phase 2 study to evaluate safety and efficacy of the total neoadjuvant therapy of short course radiation therapy followed by neoadjuvant oxaliplatin/fluorouracil-based chemotherapy (CAPOX) for cT2 rectal cancer

Condition or Disease	Intervention/Treatment	Phase
Rectal Cancer	Radiation: Radiation Drug: Chemotherapy Procedure: Surgery	Phase 2

Detailed Description

To evaluate the efficacy and safety of preoperative radiation therapy followed by preoperative chemotherapy and surgery for T2 advanced rectal cancer.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

45 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Intervention Model Description:

RT→Chemo→SurgeryRT→Chemo→Surgery

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Multicenter Single-arm Phase 2 Study to Evaluate Safety and Efficacy of the Total Neoadjuvant Therapy of Short Course Radiation Therapy Followed by Neoadjuvant Oxaliplatin/Fluorouracil-based Chemotherapy (CAPOX) for cT2 Rectal Cancer.

Actual Study Start Date :

May 25, 2023

Anticipated Primary Completion Date :

Mar 31, 2026

Anticipated Study Completion Date :

Mar 31, 2030

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TNT Neoadjuvant radiation therapy : 5Gyx5 Neoadjuvant chemo therapy : CAPOX (Oxaliplatin 130mg/m2, Capecitabine2000mg/m2/day, d1-14, 3week)x6cycles Operation: Total methorectum excision wiht radical lymph node dissection	Radiation: Radiation Neoadjuvant radiation therapy : 5Gyx5 Drug: Chemotherapy CAPOX (Oxaliplatin 130mg/m2, Capecitabine2000mg/m2/day, d1-14, 3week)x6cycles Procedure: Surgery Operation: Total methorectum excision wiht radical lymph node dissection

Arm

Intervention/Treatment

Experimental: TNT

Neoadjuvant radiation therapy : 5Gyx5 Neoadjuvant chemo therapy : CAPOX (Oxaliplatin 130mg/m2, Capecitabine2000mg/m2/day, d1-14, 3week)x6cycles Operation: Total methorectum excision wiht radical lymph node dissection

Radiation: Radiation

Neoadjuvant radiation therapy : 5Gyx5

Drug: Chemotherapy

CAPOX (Oxaliplatin 130mg/m2, Capecitabine2000mg/m2/day, d1-14, 3week)x6cycles

Procedure: Surgery

Operation: Total methorectum excision wiht radical lymph node dissection

Outcome Measures

Primary Outcome Measures

Pathological complete response (pCR) [through study completion, an average of 6 months]
pCR is evaluated by using the grading scale according to the Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

1. The patient has been fully informed of the contents of the study and has given written consent.

The patient has adenocarcinoma of the rectum confirmed by histological examination.
No distant metastases are detected on imaging studies, and radical resection is clinically feasible.
Age of 20 years or older on the date of consent. 5. ECOG Performance Status (PS) is 0 - 1 (PS 0 for age 71 years or older on the date of consent).
Previously untreated rectal cancer with the lower margin of the tumor within 12 cm of the anal verge (AV).
Patients with cT2N0M0 in the diagnosis before starting treatment (a lymph node with a short diameter of 7 mm or more is considered positive).

The conditions for lymph node metastasis shall be as follows. Contrast-enhanced CT or MRI (plain or contrast-enhanced) with a slice width of 5 mm or less.

(i) Short diameter of 10 mm or more (ii) Short diameter of 7 mm or more and one or more of the following a) to c) are met

(a) Edge irregularity (b) Low signal area with internal heterogeneity on MRI (c) Circular (long/short diameter ratio < 1.5) If contrast-enhanced CT is not possible due to contrast medium allergy, renal dysfunction, or bronchial asthma, simple CT is acceptable.

The following criteria for major organ function within 14 days prior to registration are met.

If more than one test result exists within this period, the most recent one should be used. No blood transfusions or hematopoietic factor products should be administered within 14 days prior to the test date.

Neutrophil count: greater than or equal to 1,500/mm3
Platelet count: >= 10.0 x 104 /mm3
Hemoglobin concentration: >=9.0 g/dL
Total bilirubin: 1.5 times or less than the upper limit of the institutional standard
AST, ALT, ALP: 2.5 times or less than the upper limit of the institutional standard
Serum creatinine: 1.5 times or less than the upper limit of the institutional standard or creatinine clearance: 45 mL/min or more

Exclusion Criteria:

1. underwent treatment by any of the following within a certain period of time prior to initiation of protocol therapy

extensive surgery (excluding CV port placement) within 4 weeks
Any anticancer therapy within 4 weeks
Radiation within 4 weeks 2. concomitant or pre-existing severe pulmonary disease (interstitial pneumonia, pulmonary fibrosis, severe emphysema, etc.) 3. patients who have had a colonic stent implanted 4. patients with serious comorbidities (heart failure, renal failure, liver failure, bleeding peptic ulcer, intestinal paralysis, bowel obstruction, poorly controlled diabetes, etc.) 5. patients with active multiple overlapping cancers (synchronous multiple overlapping cancers or iatrogenic multiple overlapping cancers with a disease-free period of 5 years or less). However, carcinoma in situ (intraepithelial carcinoma) or intramucosal carcinoma that is considered curable by local treatment is not considered active multiple overlapping carcinoma.
pregnant or lactating women, positive pregnancy test or unwillingness to use contraception 7. HBs antigen positive or HCV antibody positive. 8. has known human immunodeficiency virus (HIV) infection. 9. otherwise judged by the principal investigator or subinvestigator to be unsuitable for this study.